Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib

Huh, Ki Young; Hwang, Sejung; Park, Sang Yeob; Lim, Hye Jung; Jin, Miryung; Oh, Jaeseong; Yu, Kyung‐Sang; Chung, Jae Yong

doi:10.3390/pharmaceutics13050629

Cited by 3 publications

(1 citation statement)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Simultaneously, duration of therapy was reported in sorafenib, gilteritinib and quizartinib with the range of 1.94-4.6 months (Awada et al, 2005;Borthakur et al, 2011;Semrad et al, 2012;Chen et al, 2014;Lin et al, 2017;Perl et al, 2017;Cortes J. et al, 2018;Cortes JE. et al, 2018;Usuki et al, 2018;Cortes et al, 2019;Perl et al, 2019;Usuki et al, 2019;Burchert et al, 2020;Li et al, 2020;Fierro-Maya et al, 2021;Hosono et al, 2021;Huh et al, 2021;Numan et al, 2022;Dumas et al, 2023;Kudo et al, 2023).…”

Section: Efficacy Survival Outcomementioning

confidence: 99%

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Zhao,

Zhang,

Ding

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

Introduction: FLT3 mutations are closely associated with the occurrence of hematological and solid malignancies, especially with acute myeloid leukemia. Currently, several FLT3 inhibitors are in clinical trials, and some have been applied in clinic. However, the safety, efficacy and pharmacodynamics of these FLT3 inhibitors have not been systemically analyzed before.Methods: We searched and reviewed clinical trial reports on the monotherapy of 13 FLT3 inhibitors, including sorafenib, lestaurtinib, midostaurin, gilteritinib, quizartinib, sunitinib, crenolanib, tandutinib, cabozantinib, pexidartinib, pacritinib, famitinib, and TAK-659 in patients with hematological and solid malignancies before May 31, 2023.Results: Our results showed the most common adverse events (AEs) were gastrointestinal adverse reactions, including diarrhea, hand-foot syndrome and nausea, while the most common hematological AEs were febrile neutropenia, anemia, and thrombocytopenia. Based on the published data, the mean overall survival (OS) and the mean progression-free survival (PFS) were 9.639 and 5.905 months, respectively. The incidence of overall response rate (ORR), complete remission (CR), partial response (PR), and stable disease (SD) for all these FLT3 inhibitors was 29.0%, 8.7%, 16.0%, and 42.3%, respectively. The ORRs of FLT3 inhibitors in hematologic malignancies and solid tumors were 40.8% and 18.8%, respectively, indicating FLT3 inhibitors were more effective for hematologic malignancies than for solid tumors. In addition, time to maximum plasma concentration (Tmax) in these FLT3 inhibitors ranged from 0.7-12.0 hours, but the elimination half-life (T1/2) range was highly variable, from 6.8 to 151.8 h.Discussion: FLT3 inhibitors monotherapy has shown significant anti-tumor effect in clinic, and the effectiveness may be further improved through combination medication.

show abstract

Section: Efficacy Survival Outcomementioning

confidence: 99%

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Zhao,

Zhang,

Ding

et al. 2024

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

Comprehensive Evaluation of OATP‐ and BCRP‐Mediated Drug–Drug Interactions of Methotrexate Using Physiologically‐Based Pharmacokinetic Modeling

Hwang,

Lee,

Jang

et al. 2024

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

Methotrexate (MTX) is an antifolate agent widely used for treating conditions such as rheumatoid arthritis and hematologic cancer. This study aimed to quantitatively interpret the drug–drug interactions (DDIs) of MTX mediated by drug transporters using physiologically‐based pharmacokinetic (PBPK) modeling. An open‐label, randomized, 4‐treatment, 6‐sequence, 4‐period crossover study was conducted to investigate the effects of rifampicin (RFP), an inhibitor of organic anionic transporting peptides (OATP) 1B1/3, and febuxostat (FBX), an inhibitor of breast cancer resistance protein (BCRP), on the pharmacokinetics of MTX in healthy volunteers. PBPK models of MTX, RFP, and FBX were developed based on in vitro and in vivo data, and the performance of the simulation results for final PBPK models was validated in a clinical study. In the clinical study, when MTX was co‐administered with RFP or FBX, systemic exposure of MTX increased by 33% and 17%, respectively, compared with that when MTX was administered alone. When MTX was co‐administered with RFP and FBX, systemic exposure increased by 52% compared with that when MTX was administered alone. The final PBPK model showed a good prediction performance for the observed clinical data. The PBPK model of MTX was well developed in this study and can be used as a potential mechanistic model to predict and evaluate drug transporter‐mediated DDIs of MTX with other drugs.

show abstract

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model

Yang,

Li,

et al. 2023

CPD

View full text Add to dashboard Cite

Objectives:: Cyclosporin is one of the therapeutic regimens for hemophagocytic lymphohistiocytosis (HLH); however, the optimal dosage of cyclosporine in children with HLH is unknown. It has been found that piperacillin-tazobactam affects the cyclosporine pharmacokinetic process in pediatric HLH patients. Thus, the purpose of the present study was to recommend cyclosporin dosage for pediatric HLH with and without piperacillin- tazobactam. Methods:: A previously established cyclosporine population pharmacokinetic model for pediatric HLH patients has been used in this study to recommend optimal dosage based on Monte Carlo simulation. The pediatric HLH patients have been included in eight weight groups (5, 10, 20, 30, 40, 50, 60, 70 kg) for sixteen dosages (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 mg/kg), split into one dose or two doses. Results:: The optimal cyclosporin dosages for children having HLH without piperacillin-tazobactam have been found to be 15, 13, 12, 11, 10, and 9 mg/kg, split into two doses for weights of 5-7, 7-10, 10-20, 20-28, 28-45, and 45-70 kg, respectively. For children with HLH, optimal cyclosporin dosages with piperacillin-tazobactam have been found to be 8 and 7 mg/kg, split into two doses for weights of 5-20 and 20-70 kg, respectively. Conclusion: It is the first time that the cyclosporin dosage regimens for HLH in children have been developed based on Monte Carlo simulation, and the initial dosage optimizations of cyclosporine in pediatric HLH patients have been recommended.

show abstract

Population Pharmacokinetic Modelling and Simulation to Determine the Optimal Dose of Nanoparticulated Sorafenib to the Reference Sorafenib

Cited by 3 publications

References 27 publications

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Efficacy and safety of FLT3 inhibitors in monotherapy of hematological and solid malignancies: a systemic analysis of clinical trials

Comprehensive Evaluation of OATP‐ and BCRP‐Mediated Drug–Drug Interactions of Methotrexate Using Physiologically‐Based Pharmacokinetic Modeling

The Dosage Recommendation of Cyclosporin in Children with Hemophagocytic Lymphohistiocytosis based on Population Pharmacokinetic Model

Contact Info

Product

Resources

About